1. Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9
- Author
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Rita Polito, Ersilia Nigro, Filippo Scialò, Marta Mallardo, Andrea Bianco, Aurora Daniele, Nigro, E., Mallardo, M., Polito, R., Scialo, F., Bianco, A., and Daniele, A.
- Subjects
0301 basic medicine ,Leptin ,Vascular Endothelial Growth Factor A ,AdipoRon ,cell migration ,Angiogenesis ,Chemokine CXCL1 ,Adipose tissue ,chemistry.chemical_compound ,angiogenesis ,0302 clinical medicine ,Cell Movement ,Biology (General) ,Spectroscopy ,Cells, Cultured ,Tube formation ,Cultured ,Chemistry ,General Medicine ,Computer Science Applications ,Vascular endothelial growth factor A ,Angiogenesi ,Matrix Metalloproteinase 9 ,HUVEC endothelial cell ,030220 oncology & carcinogenesis ,Matrix Metalloproteinase 2 ,Adiponectin ,hormones, hormone substitutes, and hormone antagonists ,Human ,medicine.medical_specialty ,QH301-705.5 ,Human Umbilical Vein Endothelial Cell ,Adipokine ,Neovascularization, Physiologic ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Internal medicine ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Physical and Theoretical Chemistry ,Physiologic ,QD1-999 ,Molecular Biology ,Neovascularization ,Organic Chemistry ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Cell ,HUVEC endothelial cells - Abstract
Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration, after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration, interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel’s formation, to candidate them as therapeutic targets.
- Published
- 2021